PNPH_MOUSE
ID PNPH_MOUSE Reviewed; 289 AA.
AC P23492; Q4FJT6;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Purine nucleoside phosphorylase;
DE Short=PNP;
DE EC=2.4.2.1 {ECO:0000305|PubMed:10859343, ECO:0000305|PubMed:22521465};
DE AltName: Full=Inosine phosphorylase;
DE AltName: Full=Inosine-guanosine phosphorylase;
GN Name=Pnp; Synonyms=Np, Pnp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1902950; DOI=10.1093/nar/19.7.1708;
RA Jenuth J.P., Snyder F.F.;
RT "Nucleotide sequence of murine purine nucleoside phosphorylase cDNA.";
RL Nucleic Acids Res. 19:1708-1708(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=1374046; DOI=10.1016/0378-1119(92)90398-9;
RA Nelson D.M., Foresman M.D., Ronnei B.J., McIvor R.S.;
RT "Isolation and expression of a murine purine nucleoside phosphorylase-
RT encoding cDNA and sequence similarity with the human message.";
RL Gene 113:215-221(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HEHA, MOLF/EiJ, and SPRET-1; TISSUE=Liver;
RX PubMed=7903568; DOI=10.1007/bf00361392;
RA Jenuth J.P., Mangat R.K., Snyder F.F.;
RT "cDNA sequence of four purine nucleoside phosphorylase (Np) alleles in the
RT mouse.";
RL Mamm. Genome 4:598-603(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland, and Mesenchymal cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 134-148, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=10859343; DOI=10.1084/jem.191.12.2197;
RA Arpaia E., Benveniste P., Di Cristofano A., Gu Y., Dalal I., Kelly S.,
RA Hershfield M., Pandolfi P.P., Roifman C.M., Cohen A.;
RT "Mitochondrial basis for immune deficiency. Evidence from purine nucleoside
RT phosphorylase-deficient mice.";
RL J. Exp. Med. 191:2197-2208(2000).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22521465; DOI=10.1016/j.nbd.2012.04.001;
RA Mansouri A., Min W., Cole C.J., Josselyn S.A., Henderson J.T., van Eede M.,
RA Henkelman R.M., Ackerley C., Grunebaum E., Roifman C.M.;
RT "Cerebellar abnormalities in purine nucleoside phosphorylase deficient
RT mice.";
RL Neurobiol. Dis. 47:201-209(2012).
CC -!- FUNCTION: Catalyzes the phosphorolytic breakdown of the N-glycosidic
CC bond in the beta-(deoxy)ribonucleoside molecules, with the formation of
CC the corresponding free purine bases and pentose-1-phosphate
CC (PubMed:10859343) (Probable). Preferentially acts on 6-oxopurine
CC nucleosides including inosine and guanosine (Probable).
CC {ECO:0000269|PubMed:10859343, ECO:0000305|PubMed:10859343,
CC ECO:0000305|PubMed:22521465}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=inosine + phosphate = alpha-D-ribose 1-phosphate +
CC hypoxanthine; Xref=Rhea:RHEA:27646, ChEBI:CHEBI:17368,
CC ChEBI:CHEBI:17596, ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC Evidence={ECO:0000305|PubMed:10859343, ECO:0000305|PubMed:22521465};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine + phosphate = alpha-D-ribose 1-phosphate + guanine;
CC Xref=Rhea:RHEA:13233, ChEBI:CHEBI:16235, ChEBI:CHEBI:16750,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC Evidence={ECO:0000305|PubMed:10859343};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyguanosine + phosphate = 2-deoxy-alpha-D-ribose 1-
CC phosphate + guanine; Xref=Rhea:RHEA:27738, ChEBI:CHEBI:16235,
CC ChEBI:CHEBI:17172, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1;
CC Evidence={ECO:0000305|PubMed:10859343};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyinosine + phosphate = 2-deoxy-alpha-D-ribose 1-
CC phosphate + hypoxanthine; Xref=Rhea:RHEA:27750, ChEBI:CHEBI:17368,
CC ChEBI:CHEBI:28997, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1;
CC Evidence={ECO:0000305|PubMed:10859343};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000269|PubMed:10859343}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:P00491}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P00491}.
CC -!- POLYMORPHISM: Four electrophoretic alleles of NP are known; NPA (shown
CC here), NPB, NPC and NPD.
CC -!- DISRUPTION PHENOTYPE: At 10-week old, mice have a smaller cerebellum,
CC corpus callosum and thalamus and motor abnormalities (PubMed:22521465).
CC Normal number of Purkinje cells in the cerebellum at birth but numbers
CC start to decrease as mice get older (PubMed:22521465). Purkinje cells
CC in the cerebellum have an irregular shape, a granular cytoplasm and
CC degenerated dendrites characterized by fewer dendritic spines processes
CC (PubMed:22521465). Loss of inosine phosphorylase activity in
CC cerebellum, liver and kidney (PubMed:22521465). In the thymus, causes a
CC 2-fold increase in the frequency of immature CD4(-) CD8(-) double
CC negative (DN) thymocytes and a decrease in the total cell numbers of
CC CD4(+)CD8(+) double positive (DP), and CD4(+) and CD8(+) single
CC positive (SP) thymocytes due to an increase in apoptosis
CC (PubMed:10859343). In the spleen and lymph nodes, numbers of CD4(+) and
CC CD8(+) T-cells are reduced and the frequency of immature CD19(+)IgM(+)
CC pre-B cells is increased without affecting the frequency of IgM(+)
CC mature B-cells (PubMed:10859343). In the spleen, numbers of myeloid
CC cells are also increased (PubMed:10859343). In thymocytes,
CC mitochondrial dGTP levels are increased, and GTP levels and
CC deoxyguanosine kinase activity are reduced (PubMed:10859343).
CC Accumulation of dGTP in the mitochondria of thymocytes is probably
CC causing thymocyte apoptosis by interfering with the repair of
CC mitochondrial DNA damage (PubMed:10859343). Cytotoxic T-cells-mediated
CC killing is impaired in absence of IL2 (PubMed:10859343). In urine,
CC levels of inosine, deoxyinosine, guanosine, and deoxyguanosine are
CC increased (PubMed:10859343). {ECO:0000269|PubMed:10859343,
CC ECO:0000269|PubMed:22521465}.
CC -!- SIMILARITY: Belongs to the PNP/MTAP phosphorylase family.
CC {ECO:0000305}.
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DR EMBL; X56548; CAA39888.1; -; mRNA.
DR EMBL; M84563; AAA39835.1; -; mRNA.
DR EMBL; L11290; AAC37634.1; -; mRNA.
DR EMBL; L11291; AAC37635.1; -; mRNA.
DR EMBL; L11292; AAC37706.1; -; mRNA.
DR EMBL; U35374; AAB60510.1; -; mRNA.
DR EMBL; CT010316; CAJ18524.1; -; mRNA.
DR EMBL; BC003788; AAH03788.1; -; mRNA.
DR EMBL; BC052679; AAH52679.1; -; mRNA.
DR CCDS; CCDS27029.1; -.
DR PIR; I57010; I57010.
DR PIR; I76672; I76672.
DR RefSeq; NP_038660.1; NM_013632.4.
DR AlphaFoldDB; P23492; -.
DR SMR; P23492; -.
DR BioGRID; 202284; 13.
DR STRING; 10090.ENSMUSP00000043926; -.
DR BindingDB; P23492; -.
DR ChEMBL; CHEMBL2215; -.
DR iPTMnet; P23492; -.
DR PhosphoSitePlus; P23492; -.
DR SwissPalm; P23492; -.
DR EPD; P23492; -.
DR jPOST; P23492; -.
DR MaxQB; P23492; -.
DR PaxDb; P23492; -.
DR PeptideAtlas; P23492; -.
DR PRIDE; P23492; -.
DR ProteomicsDB; 289846; -.
DR DNASU; 18950; -.
DR GeneID; 18950; -.
DR KEGG; mmu:18950; -.
DR CTD; 4860; -.
DR MGI; MGI:97365; Pnp.
DR eggNOG; KOG3984; Eukaryota.
DR InParanoid; P23492; -.
DR OrthoDB; 1078969at2759; -.
DR PhylomeDB; P23492; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-74217; Purine salvage.
DR Reactome; R-MMU-74259; Purine catabolism.
DR UniPathway; UPA00606; -.
DR BioGRID-ORCS; 18950; 3 hits in 109 CRISPR screens.
DR PRO; PR:P23492; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P23492; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0047975; F:guanosine phosphorylase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0001882; F:nucleoside binding; ISO:MGI.
DR GO; GO:0042301; F:phosphate ion binding; ISO:MGI.
DR GO; GO:0002060; F:purine nucleobase binding; ISO:MGI.
DR GO; GO:0004731; F:purine-nucleoside phosphorylase activity; IDA:MGI.
DR GO; GO:0006154; P:adenosine catabolic process; IDA:MGI.
DR GO; GO:0000255; P:allantoin metabolic process; IDA:MGI.
DR GO; GO:0046632; P:alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0006196; P:AMP catabolic process; IDA:MGI.
DR GO; GO:0044209; P:AMP salvage; IDA:MGI.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IMP:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0046059; P:dAMP catabolic process; IMP:MGI.
DR GO; GO:0006157; P:deoxyadenosine catabolic process; IMP:MGI.
DR GO; GO:0006161; P:deoxyguanosine catabolic process; IMP:MGI.
DR GO; GO:0006149; P:deoxyinosine catabolic process; IMP:MGI.
DR GO; GO:0046055; P:dGMP catabolic process; IMP:MGI.
DR GO; GO:0046070; P:dGTP metabolic process; IMP:MGI.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0046038; P:GMP catabolic process; IMP:MGI.
DR GO; GO:0006202; P:GMP catabolic process to guanine; IMP:MGI.
DR GO; GO:0032263; P:GMP salvage; IDA:MGI.
DR GO; GO:0006183; P:GTP biosynthetic process; IMP:MGI.
DR GO; GO:0046115; P:guanosine catabolic process; IMP:MGI.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0006204; P:IMP catabolic process; IMP:MGI.
DR GO; GO:0032264; P:IMP salvage; IDA:MGI.
DR GO; GO:0006148; P:inosine catabolic process; IDA:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IMP:MGI.
DR GO; GO:0006738; P:nicotinamide riboside catabolic process; ISO:MGI.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; ISO:MGI.
DR GO; GO:0009165; P:nucleotide biosynthetic process; ISO:MGI.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IMP:MGI.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:MGI.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:MGI.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IMP:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:MGI.
DR GO; GO:0042278; P:purine nucleoside metabolic process; IDA:MGI.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR GO; GO:0043101; P:purine-containing compound salvage; ISO:MGI.
DR GO; GO:0010332; P:response to gamma radiation; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0070231; P:T cell apoptotic process; IMP:MGI.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR GO; GO:0034418; P:urate biosynthetic process; IMP:MGI.
DR CDD; cd09009; PNP-EcPNPII_like; 1.
DR Gene3D; 3.40.50.1580; -; 1.
DR InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR InterPro; IPR011270; Pur_Nuc_Pase_Ino/Guo-sp.
DR InterPro; IPR011268; Purine_phosphorylase.
DR InterPro; IPR018099; Purine_phosphorylase-2_CS.
DR PANTHER; PTHR11904; PTHR11904; 1.
DR Pfam; PF01048; PNP_UDP_1; 1.
DR PIRSF; PIRSF000477; PurNPase; 1.
DR SUPFAM; SSF53167; SSF53167; 1.
DR TIGRFAMs; TIGR01700; PNPH; 1.
DR TIGRFAMs; TIGR01697; PNPH-PUNA-XAPA; 1.
DR PROSITE; PS01240; PNP_MTAP_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Glycosyltransferase;
KW Purine salvage; Reference proteome; Transferase.
FT CHAIN 1..289
FT /note="Purine nucleoside phosphorylase"
FT /id="PRO_0000184537"
FT BINDING 33
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 64
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 84..86
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 88
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 116
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 201
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 219
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 220
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 243
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 257
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT SITE 243
FT /note="Important for substrate specificity"
FT /evidence="ECO:0000250|UniProtKB:P00491"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P00491"
FT VARIANT 22
FT /note="E -> K (in haplotype NPD)"
FT VARIANT 39
FT /note="T -> A (in haplotype NPD)"
FT VARIANT 152
FT /note="D -> E (in haplotype NPD)"
FT VARIANT 176
FT /note="T -> S (in haplotype NPB)"
FT VARIANT 258
FT /note="M -> K (in haplotype NPC)"
SQ SEQUENCE 289 AA; 32277 MW; DE7C1C2B004A1113 CRC64;
MENEFTYEDY ETTAKWLLQH TEYRPQVAVI CGSGLGGLTA HLKEAQIFDY NEIPNFPQST
VQGHAGRLVF GLLNGRCCVM MQGRFHMYEG YSLSKVTFPV RVFHLLGVET LVVTNAAGGL
NPNFEVGDIM LIRDHINLPG FCGQNPLRGP NDERFGVRFP AMSDAYDRDM RQKAFTAWKQ
MGEQRKLQEG TYVMLAGPNF ETVAESRLLK MLGADAVGMS TVPEVIVARH CGLRVFGFSL
ITNKVVMDYE NLEKANHMEV LDAGKAAAQT LERFVSILME SIPLPDRGS
